The discovery of the “buckyball” by Smalley et al. at Rice in 1985 and its cousin the single-walled carbon nanotube (SWNT) by Sumio Iijima in 1991 has sparked two decades of intense research on possible applications of these novel nanostructures. SWNTs have useful properties, such as high tensile strength, low density, high electrical conductivity, and high thermal conductivity. SWNTs have demonstrated the ability to translocate into cells opening the possibility of intracellular diagnostic and therapeutic applications.
One such application, computed tomography (CT), sometimes known as computed axial tomography (CAT), is a powerful diagnostic imaging tool utilized in thousands of diagnoses annually. In CT, imaging is achieved by measuring the attenuation of an X-ray, defined as the loss of energy of the radiant beam due to absorption, scattering, and beam divergence as it propagates through a medium. X-ray slice data is generated by rotating an X-ray source around an object. Detectors opposite the source measure the intensity of the exiting X-ray, which is directly proportional to the radiodensity of the scanned object. The X-ray slices can then be reconstructed into a three-dimensional image for interpretation. Naturally radiodense objects, such as bone, can be easily distinguished from fatty tissue using unenhanced CT. However, for objects with similar radiodensities, such as cancerous tissue compared to healthy tissue, a contrast agent usually needs to be employed to achieve the correct diagnosis.
The majority of existing commercial CT contrast agents are iodine-based because of two factor: iodine is an effective X-ray scatterer due to its large number of electrons (atomic number 53) and current clinical CT X-ray sources operate at 33 keV, an energy which is also absorbed by the iodine atoms; thereby improving the overall performance of the contrast agent. The increase in attenuation at 33 keV for iodine is due to the photoelectric absorption of X-rays at that specific energy by iodine inner-shell electrons.
Many existing CT contrast agents consist of a 1,3,5 tri-iodo benzene backbone with the other three positions on the benzene ring consisting of water-solubilizing groups containing alcohol, amine, amide, and carbonyl functional groups. The major difference between the various contrast agents on the market is the structure of the water-solubilizing groups, but the tri-iodo benzene backbone is nearly universal. These CT agents contain between 25 and 50 percent by mass iodine, have high water solubility, on the order of 150 mg/mL, and are known as blood pool agents. This means the agent circulates in the blood pool, but does not translocate into the interior of cells. Sufficient contrast is achieved solely because abnormal tissues, such as cancerous tumors, require increased blood flow to sustain their growth, resulting in higher local concentrations of contrast agent. Current CT contrast agents are generally not targeted to specific cell types which lead to limitations in the detection of diseases such as vulnerable plaque in the coronary artery.